Intracellular protein receptors have been identified for steroid hormones and polycyclic aromatic compounds. These compounds bind to their respective receptors; the ligand-receptor complexes interact with DNA and activate transcription of "target" genes such as cytochrome P450. The steroid hormone receptor gene family comprises homologous genes that code for at least three different steroid hormone receptors and the oncogene erbA. The aromatic hydrocarbon (Ah) receptor gene may also be a member of this gene family. We have previously demonstrated interesting genetic and biochemical differences between the Ah receptor and steroid hormone receptors. During the past year, we have completed 'mapping' of proteolytic products of the glucocorticoid receptor and have identified a unique cysteinyl residue at the C-terminus of the receptor which reacts covalently with the affinity labeling steroid [3H]dexamethasone 21-mesylate. We have established within the LDP a S. cerevisiae cDNA expression system which we have used to express mouse and rat P450 cDNA, and which we will use also for expression of receptor cDNA clones. The availability of such an expression system should permit rapid screening of cDNA clones for TCDD-binding activity. We are currently pursuing the possibility that the Ah receptor shares homology with several domains that are conserved among estrogen, progesterone and glucocorticoid receptors from various species.